Novel glue for cartilage repair

ABSTRACT

The invention is directed toward a sterile cartilage defect implant material comprising milled lyophilized allograft cartilage pieces ranging from 0.01 mm to 1.0 mm in size in a bioabsorbable carrier taken from a group consisting of sodium hyaluronate, hyaluronic acid and its derivatives, gelatin, collagen, chitosan, alginate, buffered PBS, Dextran or polymers with allogenic chondrocytes or bone marrow cells in an amount exceeding the natural occurrence of same in hyaline cartilage and adding a cell growth additive.

RELATED APPLICATIONS

[0001] There is no related application.

FIELD OF INVENTION

[0002] The present invention is generally directed toward an implant andis more specifically directed toward a paste or gel implant material fora cartilage defect.

BACKGROUND OF THE INVENTION

[0003] Articular cartilage injury and degeneration present medicalproblems to the general population which are addressed by orthopedicsurgeons. Every year in the United States, over 500,000 arthroplastic orjoint repair procedures are performed. These include approximately125,000 total hip and 150,000 total knee arthroplastics and over 41,000open arthroscopic procedures to repair cartilaginous defects of theknee.

[0004] In the knee joint, the articular cartilage tissue forms a liningwhich faces the joint cavity on one side and is linked to thesubchondral bone plate by a narrow layer of calcified cartilage tissueon the other. Articular cartilage (hyaline cartilage) consists primarilyof extracellular matrix with a sparse population of chondrocytesdistributed throughout the tissue. Articular cartilage is composed ofchondrocytes, type II collagen fibril network, proteoglycans and water.Active chondrocytes are unique in that they have a relatively lowturnover rate and are sparsely distributed within the surroundingmatrix. The collagens give the tissue its form and tensile strength andthe interaction of proteoglycans with water give the tissue itsstiffniess to compression, resilience and durability. The hyalinecartilage provides a low friction bearing surface over the bony parts ofthe joint. If the lining becomes worn or damaged resulting in lesions,joint movement may be painful or severely restricted. Whereas damagedbone typically can regenerate successfully, hyaline cartilageregeneration is quite limited because of it's limited regenerative andreparative abilities.

[0005] Articular cartilage lesions generally do not heal, or heal onlypartially under certain biological conditions due to the lack of nerves,blood vessels and a lymphatic system. The limited reparativecapabilities of hyaline cartilage usually results in the generation ofrepair tissue that lacks the structure and biomechanical properties ofnormal cartilage. Generally, the healing of the defect results in afibrocartilaginous repair tissue that lacks the structure and biomedicalproperties of hyaline cartilage and degrades over the course of time.Articular cartilage lesions are frequently associated with disabilityand with symptoms such as joint pain, locking phenomena and reduced ordisturbed function. These lesions are difficult to treat because of thedistinctive structure and function of hyaline cartilage. Such lesionsare believed to progress to severe forms of osteoarthritis.Osteoarthritis is the leading cause of disability and impairment inmiddle-aged and older individuals, entailing significant economic,social and psychological costs. Each year, osteoarthritis accounts foras many as 39 million physician visits and more than 500,000hospitalizations. By the year 2020, arthritis is expected to affectalmost 60 million persons in the United States and to limit the activityof 11.6 million persons.

[0006] There are many current therapeutic methods being used. None ofthese therapies has resulted in the successful regeneration ofhyaline-like tissue that withstands normal joint loading and activityover prolonged periods. Currently, the techniques most widely utilizedclinically for cartilage defects and degeneration are not articularcartilage substitution procedures, but rather lavage, arthroscopicdebridement, and repair stimulation. The direct transplantation of cellsor tissue into a defect and the replacement of the defect with biologicor synthetic substitutions presently accounts for only a smallpercentage of surgical interventions. The optimum surgical goal is toreplace the defects with cartilage-like substitutes so as to providepain relief, reduce effusions and inflammation, restore function, reducedisability and postpone or alleviate the need for prostheticreplacement.

[0007] Lavage and arthroscopic debridement involve irrigation of thejoint with solutions of sodium chloride, Ringer or Ringer and lactate.The temporary pain relief is believed to result from removingdegenerative cartilage debris, proteolytic enzymes and inflammatorymediators. These techniques provide temporary pain relief, but havelittle or no potential for further healing.

[0008] Repair stimulation is conducted by means of drilling, abrasionarthroplasty or microfracture. Penetration into the subchondral boneinduces bleeding and fibrin clot formation which promotes initialrepair, however, the tissue formed is fibrous in nature and not durable.Pain relief is temporary as the tissue exhibits degeneration, loss ofresilience, stiffness and wear characteristics over time.

[0009] The periosteum and perichondrium have been shown to containmesenchymal progenitor cells capable of differentiation andproliferation. They have been used as grafts in both animal and humanmodels to repair articular defects. Few patients over 40 years of agehave obtained good clinical results, which most likely reflects thedecreasing population of osteochondral progenitor cells with increasingage. There have also been problems with adhesion and stability of thegrafts, which result in their displacement or loss from the repair site.

[0010] Transplantation of cells grown in culture provides another methodof introducing a new cell population into chondral and osteochondraldefects. Carticel® is a commercial process to culture a patient's owncartilage cells for use in the repair of cartilage defects in thefemoral condyle marketed by Genzyme Biosurgery in the United States andEurope. The procedure uses arthroscopy to take a biopsy from a healthy,less loaded area of articular cartilage. Enzymatic digestion of theharvested tissue releases the cells that are sent to a laboratory wherethey are grown for a period ranging from 2-5 weeks. Once cultivated, thecells are injected during a more open and extensive knee procedure intoareas of defective cartilage where it is hoped that they will facilitatethe repair of damaged tissue. An autologous periosteal flap with cambiumlayer is used to seal the transplanted cells in place and act as amechanical barrier. Fibrin glue is used to seal the edges of the flap.This technique preserves the subchondral bone plate and has reported ahigh success rate. Proponents of this procedure report that it producessatisfactory results, including the ability to return to demandingphysical activities, in more than 90% of patients and that biopsyspecimens of the tissue in the graft sites show hyaline-like cartilagerepair. More work is needed to assess the function and durability of thenew tissue and determine whether it improves joint function and delaysor prevents joint degeneration. As with the perichondrial graft,patient/donor age may compromise the success of this procedure aschondrocyte population decreases with increasing age. Disadvantages tothis procedure include the need for two separate surgical procedures,potential damage to surrounding cartilage when the periosteal patch issutured in place, the requirement of demanding microsurgical techniques,and the expensive cost of the procedure which is currently not coveredby insurance.

[0011] Osteochondral transplantation or mosaicplasty involves excisingall injured or unstable tissue from the articular defect and creatingcylindrical holes in the base of the defect and underlying bone. Theseholes are filled with autologous cylindrical plugs of healthy cartilageand bone in a mosaic fashion. The osteochondral plugs are harvested froma lower weight-bearing area of lesser importance in the same joint. Thistechnique, shown in Prior Art FIG. 2, can be performed as arthroscopicor open procedures. Reports of results of osteochondral plug autograftsin a small number of patients indicate that they decrease pain andimprove joint function, however, long-term results have not beenreported. Factors that can compromise the results include donor sitemorbidity, effects of joint incongruity on the opposing surface of thedonor site, damage to the chondrocytes at the articular margins of thedonor and recipient sites during preparation and implantation, andcollapse or settling of the graft over time. The limited availability ofsites for harvest of osteochondral autografts restricts the use of thisapproach to treatment of relatively small articular defects and thehealing of the chondral portion of the autograft to the adjacentarticular cartilage remains a concern.

[0012] Transplantation of large allografts of bone and overlyingarticular cartilage is another treatment option that involves a greaterarea than is suitable for autologous cylindrical plugs, as well as for anon-contained defect. The advantages of osteochondral allografts are thepotential to restore the anatomic contour of the joint, lack ofmorbidity related to graft harvesting, greater availability thanautografts and the ability to prepare allografts in any size toreconstruct large defects. Clinical experience with fresh and frozenosteochondral allografts shows that these grafts can decrease jointpain, and that the osseous portion of an allograft can heal to the hostbone and the chondral portion can function as an articular surface.Drawbacks associated with this methodology in the clinical situationinclude the scarcity of fresh donor material and problems connected withthe handling and storage of frozen tissue. Fresh allografts carry therisk of immune response or disease transmission. MusculoskeletalTransplant Foundation (MTF) has preserved fresh allografts in a mediathat maintains a cell viability of 50% for 35 days for use as implants.Frozen allografts lack cell viability and have shown a decreased amountof proteoglycan content which contribute to deterioration of the tissue.

[0013] A number of patents in the prior art show the use of bone putty,pastes or gels to fill bone defects. U.S. Pat. No. 5,290,558 issued Mar.1, 1994 discloses a flowable demineralized bone powder composition usingan osteogenic bone powder with large particle size ranging from about0.1 to about 1.2 cm. mixed with a low molecular weight polyhydroxycompound possessing from 2 to about 18 carbons including a number ofclasses of different compounds such as monosaccharides, disaccharides,water dispersible oligosaccharides and polysaccharides.

[0014] A bone gel is disclosed in the U.S. Pat. No. 5,073,373 issuedDec. 17, 1991. Bone lamellae in the shape of threads or filamentsretaining low molecular weight glycerol carrier are disclosed in U.S.Pat. Nos. 5,314,476 issued May 24, 1994 and 5,507,813 issued Apr. 16,1996 and the tissue forms described in these patents are knowncommercially as the GRAFTON® Putty and Flex, respectively.

[0015] U.S. Pat. No. 5,356,629 issued Oct. 18, 1994 discloses making arigid gel in the nature of a bone cement to fill defects in bone bymixing biocompatible particles, preferably polymethylmethacrylate coatedwith polyhydroxyethylmethacrylate in a matrix selected from a groupwhich lists hyaluronic acid to obtain a molded semi-solid mass which canbe suitably worked for implantation into bone. The hyaluronic acid canalso be utilized in monomeric form or in polymeric form preferablyhaving a molecular weight not greater than about one million Daltons. Itis noted that the nonbioabsorbable material which can be used to formthe biocompatible particles can be derived from xenograft bone,homologous bone, autogenous bone as well as other materials. Thebioactive substance can also be an osteogenic agent such asdemineralized bone powder, morselized cancellous bone, aspirated bonemarrow and other autogenous bone sources. The average size of theparticles employed is preferably about 0.1 to about 3.0 mm, morepreferably about 0.2 to about 1.5 mm, and most preferably about 0.3 toabout 1.0 mm. It is inferentially mentioned but not taught thatparticles having average sizes of about 7,000 to 8,000 microns, or evenas small as about 100 to 700 microns can be used.

[0016] U.S. Pat. No. 4,172,128 issued Oct. 23, 1979 discloses ademineralized bone material mixed with a carrier to reconstruct tooth orbone material by adding a mucopolysaccharide to a mineralized bonecolloidal material. The composition is formed from a demineralizedcoarsely ground bone material, which may be derived from human bones andteeth, dissolved in a solvent forming a colloidal solution to which isadded a physiologically inert polyhydroxy compound such asmucopolysaccharide or polyuronic acid in an amount which causesorientation when hydrogen ions or polyvalent metal ions are added toform a gel. The gel will be flowable at elevated temperatures above 35°C. and will solidify when brought down to body temperature. Example 25of the patent notes that mucopolysaccharides produce pronouncedionotropic effects and that hyaluronic acid is particularly responsiblefor spatial cross-linking.

[0017] U.S. Pat. No. 6,030,635 issued Feb. 29, 2000 and U.S. Pat. No.6,437,018 issued Aug. 20, 2002 are directed toward a malleable boneputty and a flowable gel composition for application to a bone defectsite to promote new bone growth at the site which utilize a new bonegrowth inducing compound of demineralized lyophilized allograft bonepowder. The bone powder has a particle size ranging from about 100 toabout 850 microns and is mixed in a high molecular weight hydrogelcarrier which contains a sodium phosphate saline buffer.

[0018] The use of implants for cartilage defects is much more limited.Aside from the fresh allograft implants and autologous implants, U.S.Pat. No. 6,110,209 issued Nov. 5, 1998 shows the use an autologousarticular cartilage cancerous bone paste to fill arthritic defects. Thesurgical technique is arthroscopic and includes debriding (shaving awayloose or fragmented articular cartilage), followed by morselizing thebase of the arthritic defect with an awl until bleeding occurs. Anosteochondral graft is then harvested from the inner rim of theintercondylar notch using a trephine. The graft is then morselized in abone graft crusher, mixing the articular cartilage with the cancellousbone. The paste is then pushed into the defect and secured by theadhesive properties of the bleeding bone. The paste can also be mixedwith a cartilage stimulating factor, a plurality of cells, or abiological glue. All patients are kept non-weight bearing for four weeksand used a continuous passive motion machine for six hours each night.Histologic appearance of the biopsies have mainly shown a mixture offibrocartilage with hyaline cartilage. Concerns associated with thismethod are harvest site morbidity and availability, similar to themosaicplasty method.

SUMMARY OF THE INVENTION

[0019] A cartilage implant material in paste or gel form for repairingarticular cartilage defects is composed of milled allograft cartilagepieces in a bioabsorbable carrier. Autologous chondrocyte in an amountexceeding the number naturally occurring in hyaline cartilage for amature adult between 20 and 55 years of age may also be applied to thematrix. Additives may be applied to the mixture in order to increasechondrocyte migration and proliferation. The implant material cansupport the addition of a variety of chondrogenic stimulating factorsincluding, but not limited to growth factors (FGF-2, FGF-5, IGF-1,TGF-β, BMP-2, BMP-7, PDGF, VEGF), human allogenic or autologouschondrocytes, human allogenic or autologous bone marrow cells, stemcells, demineralized bone matrix, insulin, insulin-like growth factor-1,transforming growth factor-B, interleukin-1 receptor antagonist,hepatocyte growth factor, platelet-derived growth factor, Indianhedgehog and parathyroid hormone-related peptide or bioactive glue.

[0020] The implant material is placed in the lesion area and may besealed with a periosteum cap.

[0021] It is an object of the invention to provide an allograft implantmaterial for joints which provides pain relief, restores normal functionand will postpone or alleviate the need for prosthetic replacement.

[0022] It is also an object of the invention to provide a cartilagerepair implant material which is easily placed in a defect area by thesurgeon using an arthroscopic, minimally invasive technique.

[0023] It is further an object of the invention to provide an allograftimplant material procedure which is applicable for both partial and fullthickness lesions.

[0024] It is yet another object of the invention to provide an allograftimplant material which facilitates growth of hyaline cartilage.

[0025] It is an additional object of the invention to provide implantpaste and gel material formulations that satisfy surgical requirementsand are made from donated human available allograft tissue, some ofwhich would otherwise be considered waste and thrown away.

[0026] These and other objects, advantages, and novel features of thepresent invention will become apparent when considered with theteachings contained in the detailed disclosure along with theaccompanying drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

[0027]FIG. 1 shows the anatomy of a knee joint with a lesion;

[0028]FIG. 2 shows a schematic mosaicplasty as known in the prior art;and

[0029]FIG. 3 shows a schematic perspective view of cartilage defectmaterial placed in a defect site with an exploded periosteum cap.

DESCRIPTION OF THE INVENTION

[0030] The terms “tissue” is used in the general sense herein to meanany transplantable or implantable tissue, the survivability of which isimproved by the methods described herein upon implantation. Inparticular, the overall durability and longevity of the implant areimproved, and host-immune system mediated responses, are substantiallyeliminated.

[0031] The terms “transplant” and “implant” are used interchangably torefer to tissue, material or cells (xenogeneic or allogeneic) which maybe introduced into the body of a patient to replace or supplement thestructure or function of the endogenous tissue.

[0032] The terms “autologous” and “autograft” refer to tissue or cellswhich originate with or are derived from the recipient, whereas theterms “allogeneic” and “allograft” refer to cells and tissue whichoriginate with or are derived from a donor of the same species as therecipient. The terms “xenogeneic” and “xenograft” refer to cells ortissue which originates with or is derived from a species other thanthat of the recipient.

[0033] The term “gel” refers to a mixture of minced or milled pretreatedallograft cartilage in a biocomposite carrier having a viscosity whichis less than and is less rigid than a mixture of minced or milledpretreated allograft cartilage in a biocompatible carrier referred to bythe terms “putty” or “paste” and contains less cartilage by weight thanputty or paste.

[0034] The present invention is directed towards a cartilage repairmaterial and method of treatment. The preferred embodiment and best modeof the invention is shown in FIG. 3. In the production of the invention,allograft hyaline cartilage is lyophilized reducing its water contentand milled for ease in application.

[0035] After washes with sterile de-ionized (DI) water, the cartilagematerial was frozen at −20° to −100° C. preferably −70° C. andlyophilized to reduce the water content within the range of about 0.1%to about 8.0%. The cartilage is frozen with liquid nitrogen and groundinto particles.

[0036] A lesion or defect is removed by cutting a bore 50 or trimming alesion in the implant area 100 and filling the bore 50 or lesion areawith a milled cartilage mixture 20 of paste or gel consisting togetherwith a biological carrier such as hyaluronic acid and its derivatives,gelatin, collagen, chitosan, alginate, buffered PBS, Dextran, orpolymers and one or more additives namely chondrogenic stimulatingfactors including, but not limited to growth factors (FGF-2, FGF-5,IGF-1, TGF-β, BMP-2, BMP-7, PDGF, VEGF), human allogenic or autologouschondrocytes, human allogenic cells, human allogenic or autologous bonemarrow cells, human allogenic or autologous stem cells, demineralizedbone matrix, insulin, insulin-like growth factor-1, interleukin-1receptor antagonist, hepatocyte growth factor, platelet-derived growthfactor, Indian hedgehog and parathyroid hormone-related peptide.

[0037] Suitable organic glue material can be used to keep the viscouscartilage mixture 20 fixed in place in the implant area or to affix aperiosteal cap 30 in place over the surrounding hyaline cartilage area100. Suitable organic glue material can be found commercially, such asfor example; TISSEEL® or TISSUCOL.®) (fibrin based adhesive; Immuno AG,Austria), Adhesive Protein (Sigma Chemical, USA), and Dow CorningMedical Adhesive B (Dow Corning, USA).

EXAMPLE 1

[0038] A matrix of minced cartilage putty consisting of minced or milledallograft articular cartilage which has been lyophilized so that itswater content ranges from 0.1% to 8.0% with a cartilage content rangingfrom 25% to 50% by weight is mixed with a carrier of sodium hyaluronatesolution (HA) (molecular weight ranging from 7.0×10⁵ to 1.2×10⁶) or anyother bioabsorbable carrier such as hyaluronic acid and its derivatives,gelatin, collagen, chitosan, alginate, buffered PBS, Dextran, orpolymers, the carrier ranging from 75% to 50% by weight. The cartilageis milled to a size ranging from 0.01 mm to 1 mm. In gel form, theminced cartilage which has been lyophilized so that its water contentranges from 0.1% to 8.0% ranging from 15% to 30% by weight and thecarrier ranges from 85% to 70% by weight. The particle size of thecartilage when milled is less than or equal to 1 mm dry in thepreviously stated range. The cartilage pieces can be processed tovarying particle sizes and the HA or other carrier can have differentviscosities depending on the desired consistency of the putty or paste.This cartilage matrix can be deposited into the cartilage defectarthroscopically and fit into the defect where it is held in place byit's own viscosity, mixed with fibrin glue or covered with a periostealor perichondrial flap, then sealed with biological glue. As with thefirst two matrices, this matrix can support the previously mentionedchondrogenic factors.

EXAMPLE 2

[0039] A matrix of minced cartilage putty consisting of minced or milledallograft cartilage which has been lyophilized so that its water contentranges from 0.1% to 8.0% ranging from 25% to 50% by weight is mixed witha carrier of sodium hyaluronate solution (HA) (7.0×10⁵ to 1.2×10⁶) orany other bioabsorbable carrier such as hyaluronic acid and itsderivatives, gelatin, collagen, chitosan, alginate, buffered PBS,Dextran, or polymers ranging from 75% to 50% by weight. In a gel form,the minced cartilage which has been lyophilized so that its watercontent ranges from 0.01% to 8.0% ranging from 15% to 30% by weight andthe carrier ranges from 85% to 70% by weight. The particle size of thecartilage is less than or equal to 1 mm dry ranging from 0.01 mm to 1mm. The cartilage pieces can be processed to varying particle sizes andthe HA or carrier can have different viscosities depending on thedesired consistency of the putty or paste. Autologous or allogenic cellswhich have been grown outside the patient are inserted by syringe intothe matrix before, during or after deposit of the cartilage matrix intothe defect area. Such cells include allogenic or autologous bone marrowcells, stem cells and chondrocyte cells. The cellular density of thecells preferably ranges from about 1×10⁸ to 5×10⁸ or from about 100million to about 500 million cells per cc of putty or gel mixture. Thiscomposite material can be injected into the cartilage defectarthroscopically and fit into the defect where it is held in place byit's own viscosity, or covered with a periosteal or perichondrial flap,then sealed with biological glue. As with the first matrix, this matrixcan support the previously mentioned chondrogenic factors.

[0040] The operation of placing the cartilage composition in a cartilagedefect, comprises (a) cutting a patient's tissue at a site of acartilage defect to remove the diseased area of cartilage; (b) placing amixture of milled allograft cartilage in a bioabsorbable carrier in thedefect area; and (c) placing a periosteal cover over the mixture of theinserted milled allograft cartilage in a bioabsorbable carrier tocontain the mixture in the defect area for a predetermined period oftime to promote cartilage growth at the defect site. Alternate stepsinclude the addition of growth factors, chondrocytes, bone marrow cellsand stem cells.

[0041] The principles, preferred embodiments and modes of operation ofthe present invention have been described in the foregoingspecification. However, the invention should not be construed as limitedto the particular embodiments which have been described above. Instead,the embodiments described here should be regarded as illustrative ratherthan restrictive. Variations and changes may be made by others withoutdeparting from the scope of the present invention as defined by thefollowing claims:

What we claim is:
 1. A sterile allograft cartilage defect implantmaterial comprising milled allograft cartilage pieces lyophilized sothat their water content ranges from about 0.1% to about 8.0% in abioabsorbable carrier.
 2. A sterile allograft cartilage defect implantmaterial as claimed in claim 1 wherein said milled cartilage pieces aresized less than 1 mm.
 3. A sterile allograft cartilage defect implantmaterial as claimed in claim 1 wherein said milled cartilage ranges fromabout 25% to about 50% by weight and said carrier ranges from about 75%to about 50% by weight.
 4. A sterile allograft cartilage defect implantmaterial as claimed in claim 1 wherein said milled cartilage ranges fromabout 15% to about 30% by weight with the carrier ranging from about 85%to about 70% by weight.
 5. A sterile allograft cartilage defect implantmaterial as claimed in claim 1 wherein said carrier is sodiumhyaluronate and its derivatives.
 6. A sterile allograft cartilage defectimplant material as claimed in claim 1 wherein said implant materialincludes a protein glue.
 7. A sterile allograft cartilage defect implantmaterial as claimed in claim 1 wherein said implant material includesautologous chondrocytes in a concentration exceeding the concentrationof chondrocytes naturally occurring in the patient.
 8. A sterileallograft cartilage defect implant material as claimed in claim 1wherein said milled cartilage is hyaline cartilage.
 9. A sterileallograft cartilage defect implant material as claimed in claim 1wherein said milled cartilage is fibrous cartilage.
 10. A sterileallograft cartilage defect implant material as claimed in claim 1wherein said milled cartilage is hyaline and fibrous cartilage.
 11. Asterile allograft cartilage defect implant material claimed in claim 1including an additive to said material consisting of one or more of agroup consisting of growth factors, human allogenic cells, humanallogenic bone marrow cells, human autologous bone marrow cells, humanallogenic stem cells, human autologous stem cells, human demineralizedbone matrix, and insulin. 12 A sterile cartilage repair material asclaimed in claim 11 wherein said growth factors are one or more of agroup consisting of FGF-2, FGF-5, IGF-1, TGF-β, BMP-2, BMP-7, PDGF,VEGF. 13 A sterile allograft cartilage defect implant material asclaimed in claim 1 wherein said carrier comprises one or more of abioabsorbable carriers taken from a group consisting of sodiumhyaluronate, hyaluronic acid and its derivatives, gelatin, collagen,chitosan, alginate, buffered PBS, Dextran or polymers.
 14. A sterilecartilage defect implant material comprising milled allograft articularcartilage pieces ranging from 0.01 mm to 1.0 mm in size in abioabsorbable carrier taken from a group consisting of sodiumhyaluronate, gelatin, collagen, chitosan, alginate, buffered PBS,Dextran or polymers and allogenic chondrocytes in an amount exceedingthe natural occurrence of same in articular cartilage.
 15. A sterilecartilage defect implant material as claimed in claim 14 wherein saidallograft articular cartilage is hyaline cartilage.
 16. A sterileallograft cartilage defect implant material as claimed in claim 14wherein said milled cartilage is fibrous cartilage.
 17. A sterileallograft cartilage defect implant material as claimed in claim 14wherein said milled cartilage is hyaline and fibrous cartilage.
 18. Asterile cartilage repair material as claimed in claim 14 wherein saidimplant material includes an additive consisting of one or more of agroup consisting of growth factors, human allogenic cells, humanallogenic bone marrow cells, human autologous bone marrow cells, humanallogenic stem cells, human autologous stem cells, demineralized bonematrix, and insulin.
 19. A sterile cartilage repair material as claimedin claim 14 wherein said growth factors are one or more of a groupconsisting of FGF-2, FGF-5, IGF-1, TGF-β, BMP-2, BMP-7, PDGF, VEGF. 20.A sterile cartilage defect implant material as claimed in claim 14wherein said milled cartilage ranges from about 25% to about 50% byweight and said carrier ranges from about 75% to about 50% by weight.21. A sterile cartilage defect implant material as claimed in claim 14wherein said milled cartilage ranges from about 15% to about 30% byweight with the carrier ranging from about 85% to about 70% by weight.22. A sterile cartilage defect implant material comprising lyophilizedmilled allograft articular cartilage pieces ranging from 0.01 mm to 1.0mm in size in a bioabsorbable carrier taken from a group consisting ofsodium hyaluronate, hyaluronic acid and its derivatives, gelatin,collagen, chitosan, alginate, buffered PBS, Dextran or polymers andautologous bone marrow cells in an amount exceeding the naturaloccurrence of same in articular cartilage.
 23. A sterile cartilagedefect repair material as claimed in claim 22 including an additive insaid implant material which consists of one or more of a groupconsisting of growth factors, human allogenic cells, autologouschondrocytes, demineralized bone matrix, and insulin.
 24. A sterilecartilage repair material as claimed in claim 14 wherein said growthfactors are one or more of a group consisting of FGF-2, FGF-5, IGF-1,TGF-β, BMP-2, BMP-7, PDGF, VEGF.
 25. A sterile cartilage defect repairmaterial as claimed in claim 22 wherein said bioabsorbable carrierconsists of sodium hyaluronate.
 26. A sterile cartilage defect materialas claimed in claim 22 wherein said cartilage pieces that have beenlyophilized to have a water content ranging from about 0.1% to 8.0%. 27.A sterile cartilage defect implant material as claimed in claim 22wherein said allograft articular cartilage is hyaline cartilage.
 28. Asterile allograft cartilage defect implant material as claimed in claim22 wherein said milled cartilage is fibrous cartilage.
 29. A sterileallograft cartilage defect implant material as claimed in claim 22wherein said milled cartilage is hyaline and fibrous cartilage.
 30. Asterile cartilage defect implant material as claimed in claim 22 whereinsaid milled cartilage ranges from about 25% to about 50% by weight andsaid carrier ranges from about 75% to about 50% by weight.
 31. A sterilecartilage defect implant material as claimed in claim 22 wherein saidmilled cartilage ranges from about 15% to about 30% by weight with thecarrier ranging from about 85% to about 70% by weight.
 33. A sterilecartilage defect implant material comprising lyophilized milledallograft articular cartilage pieces ranging from 0.01 mm to 1.0 mm insize in a bioabsorbable carrier taken from a group consisting of sodiumhyaluronate, hyaluronic acid and its derivatives, gelatin, collagen,chitosan, alginate, buffered PBS, Dextran or polymers and autologousstem cells in an amount exceeding the natural occurrence of same in apatient being treated.
 34. A method of placing a cartilage defectmaterial in a cartilage defect, said material comprising allograftarticular cartilage which has been lyophilized and mixed in abioabsorbable carrier comprising the steps of: (a) cutting patienttissue at a site of a cartilage defect to remove the diseased area ofcartilage; (b) adding autologous cells to said mixture of milledallograft cartilage in a bioabsorbable carrier; (c) placing a mixture ofmilled allograft cartilage in a bioabsorbable carrier in the area wherecartilage has been removed; (d) placing a cover over the mixture ofmilled allograft cartilage in a bioabsorbable carrier to contain themixture in cartilage defect site for a predetermined period of time. 35.The method of claim 34 wherein growth factors are added to said mixture.36. The method of claim 34 wherein said cells are chondrocytes.
 37. Themethod of claim 34 wherein said cells are bone marrow cells.
 38. Themethod of claim 34 wherein said cells are stem cells.